In order to elucidate the structure-function relationship at active sites and regulatory sites of enzymes, we determine the structures by X-ray diffraction, and bind inhibitors, transition state analogues, and substrate analogues in order to interpret reaction mechanisms and regulatory mechanisms. Proteins under study include leucine aminopeptidase(related to aging and hormone control), chorismate mutase(related to new mechanism, and to bacteriocidal, fungicidal and herbicidal materials), fructose-1,6-bisphosphatase(related to Type II diabetes), aspartate transcarbamylase(related to cancer, chemotherapy) and a DNA-(cytosine-5)-Methyltransferase(related to differentiation and regulation of gene expression. In all of these studies the structure and behavior of site specific mutants are an essential component.